Arquivos de Asma, Alergia e Imunologia
https://aaai-asbai.org.br/article/doi/10.5935/2318-5015.20140016
Arquivos de Asma, Alergia e Imunologia
Review Article

Aspectos práticos no diagnóstico e manejo das reações de hipersensibilidade a fármacos

Practical aspects in the diagnosis and management of drug hypersensitivity reactions

Ullissis P. Menezes; Daniel L. Cordeiro; Janaina Michelle L. Melo

Downloads: 0
Views: 19

Resumo

As reações de hipersensibilidade a fármacos (RHF) podem ser de natureza alérgica ou não alérgica, e correspondem a aproximadamente 15% de todas as reações adversas a fármacos (RAF). As reações alérgicas são mediadas por mecanismo imune, não previsíveis, podendo ser graves e até mesmo fatais, ou requererem internações hospitalares prolongadas. Erros na classificação das RHF ocorrem com frequência, principalmente quando o diagnóstico é baseado apenas na história clínica (superdiagnóstico) ou quando as reações não são documentadas de maneira apropriada (subdiagnóstico). O diagnóstico inadequado pode levar à exclusão desnecessária, com diminuição das opções terapêuticas, e ao uso de fármacos alternativos ineficazes e/ou de custo elevado. Os grupos de fármacos mais comumente envolvidos em reações de hipersensibilidade são os betalactâmicos e os anti-inflamatórios não esteroidais (AINEs). Consensos atuais preconizam uma investigação diagnóstica sistematizada das RHF através da realização de testes cutâneos, laboratoriais e testes de provocação, direcionados por uma história clínica detalhada. O objetivo do presente estudo é abordar aspectos práticos do diagnóstico e manejo das reações de hipersensibilidade a fármacos, com ênfase aos betalactâmicos e AINEs, de acordo com os estudos e consensos atuais.

Palavras-chave

Hipersensibilidade a drogas, alergia, imunologia.

Abstract

Drug hypersensitivity reactions (DHRs) may be classified as allergic or non-allergic, and they correspond to approximately 15% of all adverse drug reactions (ADRs). Allergic reactions are non-predictable and mediated by immune mechanisms; they may be severe and even lifethreatening, or may require prolonged hospitalization. Misclassification of DHRs is frequent, especially when diagnosis is based only on medical history (overdiagnosis), or when reactions are not properly documented (underdiagnosis). An incorrect diagnosis may lead to unnecessary exclusion of drugs, reducing treatment options, as well as to the use of alternative ineffective and/or expensive medications. Beta-lactam and non-steroidal anti-inflammatory drugs are the groups most commonly involved in DHRs. Current guidelines recommend a systematic diagnostic investigation of DHRs using skin, laboratory, and provocations tests, guided by a detailed medical history. The aim of this study was to address practical aspects of the diagnosis and management of DHRs, with a focus on beta-lactam and non-steroidal anti-inflammatory drugs, according to current studies and consensuses.

Keywords

Drug hypersensitivity, allergy, immunology.

References

1. Gomes E, Cardoso MF, Praça F, Gomes L, Mariño E, Demoly P. Selfreported drug allergy in a general adult Portuguese population. Clin Exp Allergy. 2004;34(10):1597-601.

2. Demoly P, Pichler W, Pirmohamed M, Romano A. Important questions in Allergy: 1– drug allergy/hypersensitivity. Allergy. 2008;63(5):616-9.

3. Pirmohamed M, James S, Meakin S, Green C, Scott AK, Walley TJ, et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18820 patients. BMJ. 2004;329(7456):15-9.

4. Bowman L, Carlstedt BC, Black CD. Incidence of adverse drug reactions in adult medical inpatients. Can J Hosp Pharm. 1994;47(5):209-16.

5. Demoly P, Adkinson NF, Brockow K, Castells M, Chiriac AM, Greenberger PA, et al. International Consensus on drug allergy. Allergy. 2014;69(4):420-37.

6. Mirakian R, Ewan PW, Durham SR, Youlten LJ, Dugué P, Friedmann PS, et al. BSACI guidelines for the management of drug allergy. Clin Exp Allergy. 2009;39(1):43-61.

7. Gomes ER, Demoly P. Epidemiology of hypersensitivity drug reactions. Curr Opin Allergy Clin Immunol. 2005;5(4):309-16.

8. Bircher AJ, Scherer Hofmeier K. Drug hypersensitivity reactions: Inconsistency in the use of the classification of immediate and nonimmediate reactions. J Allergy Clin Immunol. 2012;129(1):263-4; author reply 5-6.

9. Pichler WJ. Delayed drug hypersensitivity reactions. Ann Intern Med. 2003;139(8):683-93.

10. Romano A, Torres MJ, Castells M, Sanz ML, Blanca M. Diagnosis and management of drug hypersensitivity reactions. J Allergy Clin Immunol. 2011;127(3 Suppl):S67-73.

11. Demoly P, Kropf R, Bircher A, Pichler WJ. Drug hypersensitivity: questionnaire. EAACI interest group on drug hypersensitivity. Allergy. 1999;54(9):999-1003.

12. Malaman M, Rodrigues A, Felix M, Menezes U, Tanno L, CameloNunes I, et al. Recomendações para o diagnóstico das reações de hipersensibilidade imediatas aos antibióticos beta-lactâmicos. Rev bras alerg imunopatol. 2011;34:257-62.

13. Brockow K, Garvey LH, Aberer W, Atanaskovic-Markovic M, Barbaud A, Bilo MB, et al. Skin test concentrations for systemically administered drugs – an ENDA/EAACI Drug Allergy Interest Group position paper. Allergy. 2013;68(6):702-12.

14. Romano A, Blanca M, Torres MJ, Bircher A, Aberer W, Brockow K, et al. Diagnosis of nonimmediate reactions to beta-lactam antibiotics. Allergy. 2004;59(11):1153-60.

15. Barbaud A, Reichert-Penetrat S, Tréchot P, Jacquin-Petit MA, Ehlinger A, Noirez V, et al. The use of skin testing in the investigation of cutaneous adverse drug reactions. Br J Dermatol. 1998;139(1):49‑58.

16. Uyttebroek AP, Sabato V, Bridts CH, Ebo DG. In vitro diagnosis of immediate IgE-mediated drug hypersensitivity: warnings and (unmet) needs. Immunol Allergy Clin North Am. 2014;34(3):681-9, x.

17. Blanca M, Mayorga C, Torres MJ, Reche M, Moya MC, Rodriguez JL, et al. Clinical evaluation of Pharmacia CAP System RAST FEIA amoxicilloyl and benzylpenicilloyl in patients with penicillin allergy. Allergy. 2001;56(9):862-70.

18. Fontaine C, Mayorga C, Bousquet PJ, Arnoux B, Torres MJ, Blanca M, et al. Relevance of the determination of serum-specific IgE antibodies in the diagnosis of immediate beta-lactam allergy. Allergy. 2007;62(1):47-52.

19. Torres MJ, Blanca M. The complex clinical picture of beta-lactam hypersensitivity: penicillins, cephalosporins, monobactams, carbapenems, and clavams. Med Clin North Am. 2010;94(4):805‑20, xii.

20. Torres MJ, Padial A, Mayorga C, Fernández T, Sanchez-Sabate E, Cornejo-García JA, et al. The diagnostic interpretation of basophil activation test in immediate allergic reactions to betalactams. Clin Exp Allergy. 2004;34(11):1768-75.

21. Uyttebroek AP, Sabato V, Faber MA, Cop N, Bridts CH, Lapeere H, et al. Basophil activation tests: time for a reconsideration. Expert Rev Clin Immunol. 2014;10(10):1325-35.

22. Ebo DG, Leysen J, Mayorga C, Rozieres A, Knol EF, Terreehorst I. The in vitro diagnosis of drug allergy: status and perspectives. Allergy. 2011;66(10):1275-86.

23. Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol. 2010;105(4):259-73.

24. Aberer W, Bircher A, Romano A, Blanca M, Campi P, Fernandez J, et al. Drug provocation testing in the diagnosis of drug hypersensitivity reactions: general considerations. Allergy. 2003;58(9):854-63.

25. Thalayasingam M, Davies LJ, Llanora GV, Gerez IF, Van Bever HP, Shek LP. Clinical characteristics and outcomes of patients undergoing drug provocation tests (DPTs). Ann Acad Med Singapore. 2013;42(4):184-9.

26. Vezir E, Erkocoglu M, Civelek E, Kaya A, Azkur D, Akan A, et al. The evaluation of drug provocation tests in pediatric allergy clinic: a single center experience. Allergy Asthma Proc. 2014;35(2):156-62.

27. Messaad D, Sahla H, Benahmed S, Godard P, Bousquet J, Demoly P. Drug provocation tests in patients with a history suggesting an immediate drug hypersensitivity reaction. Ann Intern Med. 2004;140(12):1001-6.

28. Ponvert C, Perrin Y, Bados-Albiero A, Le Bourgeois M, Karila C, Delacourt C, et al. Allergy to betalactam antibiotics in children: results of a 20-year study based on clinical history, skin and challenge tests. Pediatr Allergy Immunol. 2011;22(4):411-8.

29. Agache I, Bilò M, Braunstahl GJ, Delgado L, Demoly P, Eigenmann P, et al. In vivo diagnosis of allergic diseases-allergen provocation tests. Allergy. 2015;70(4):355-65.

30. Rerkpattanapipat T, Chiriac AM, Demoly P. Drug provocation tests in hypersensitivity drug reactions. Curr Opin Allergy Clin Immunol. 2011;11(4):299-304.

31. Ponvert C. Diagnosis of allergic and non-allergic hypersensitivity reactions to commonly used drugs and biological substances in children: diagnostic algorithm. Arch Pediatr. 2011;18(4):486-92.

32. Demoly P, Romano A, Botelho C, Bousquet-Rouanet L, Gaeta F, Silva R, et al. Determining the negative predictive value of provocation tests with beta-lactams. Allergy. 2010;65(3):327-32.

33. Defrance C, Bousquet PJ, Demoly P. Evaluating the negative predictive value of provocation tests with nonsteroidal anti-inflammatory drugs. Allergy. 2011;66(11):1410-4.

34. Mirakian R, Leech SC, Krishna MT, Richter AG, Huber PA, Farooque S, et al. Management of allergy to penicillins and other beta-lactams. Clin Exp Allergy. 2015;45(2):300-27.

35. Soriano V, Niveiro E, Fernández J, Castelló JV, González P. Successful desensitization to penicillin after diagnostic reassessment. Allergol Immunopathol (Madr). 2003;31(2):94-6.

36. Chiriac AM, Demoly P. Drug allergy diagnosis. Immunol Allergy Clin North Am. 2014;34(3):461-71,vii.

37. Cernadas JR, Brockow K, Romano A, Aberer W, Torres MJ, Bircher A, et al. General considerations on rapid desensitization for drug hypersensitivity - a consensus statement. Allergy. 2010;65(11):1357‑66.

38. Hong DI, Dioun AF. Indications, protocols, and outcomes of drug desensitizations for chemotherapy and monoclonal antibodies in adults and children. J Allergy Clin Immunol Pract. 2014;2(1):13-9; quiz 20.

39. Castells M. Rapid desensitization for hypersensitivity reactions to medications. Immunol Allergy Clin North Am. 2009;29(3):585-606.

40. Scherer K, Brockow K, Aberer W, Gooi JH, Demoly P, Romano A, et al. Desensitization in delayed drug hypersensitivity reactions – an EAACI position paper of the Drug Allergy Interest Group. Allergy. 2013;68(7):844-52.

41. Solensky R. Allergy to β-lactam antibiotics. J Allergy Clin Immunol. 2012;130(6):1442-2.e5.

42. Khan DA, Solensky R. Drug allergy. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S126-37.

43. Blanca M, Romano A, Torres MJ, Férnandez J, Mayorga C, Rodriguez J, et al. Update on the evaluation of hypersensitivity reactions to betalactams. Allergy. 2009;64(2):183-93.

44. Romano A, Warrington R. Antibiotic allergy. Immunol Allergy Clin North Am. 2014;34(3):489-506, vii.

45. Macy E, Ngor EW. Safely diagnosing clinically significant penicillin allergy using only penicilloyl-poly-lysine, penicillin, and oral amoxicillin. J Allergy Clin Immunol Pract. 2013;1(3):258-63.

46. Bursztejn AC, Romano A, Guéant-Rodriguez RM, Cornejo JA, Oussalah A, Chery C, et al. Allergy to betalactams and nucleotide-binding oligomerization domain (NOD) gene polymorphisms. Allergy. 2013;68(8):1076-80.

47. Mori F, Cianferoni A, Barni S, Pucci N, Rossi ME, Novembre E. Amoxicillin allergy in children: five-day drug provocation test in the diagnosis of nonimmediate reactions. J Allergy Clin Immunol Pract. 2015.

48. Cornejo-Garcia JA, Blanca-López N, Doña I, Andreu I, Agúndez JA, Carballo M, et al. Hypersensitivity reactions to non-steroidal antiinflammatory drugs. Curr Drug Metab. 2009;10(9):971-80.

49. Kowalski ML, Asero R, Bavbek S, Blanca M, Blanca-Lopez N, Bochenek G, et al. Classification and practical approach to the diagnosis and management of hypersensitivity to nonsteroidal anti-inflammatory drugs. Allergy. 2013;68(10):1219-32.

50. Kowalski ML, Makowska JS, Blanca M, Bavbek S, Bochenek G, Bousquet J, et al. Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) - classification, diagnosis and management: review of the EAACI/ENDA(#) and GA2LEN/HANNA*. Allergy. 2011;66(7):818‑29.

51. Sánchez-Borges M. NSAID hypersensitivity (respiratory, cutaneous, and generalized anaphylactic symptoms). Med Clin North Am. 2010;94(4):853-64,xiii.

52. Canto MG, Andreu I, Fernandez J, Blanca M. Selective immediate hypersensitivity reactions to NSAIDs. Curr Opin Allergy Clin Immunol. 2009;9(4):293-7.

53. Ortega N, Doña I, Moreno E, Audicana MT, Barasona MJ, BergesGimeno MP, et al. Practical guidelines for diagnosing hypersensitivity reactions to nonsteroidal anti-inflammatory drugs. J Investig Allergol Clin Immunol. 2014;24(5):308-23.

54. Torres MJ, Mayorga C, Blanca M. Nonimmediate allergic reactions induced by drugs: pathogenesis and diagnostic tests. J Investig Allergol Clin Immunol. 2009;19(2):80-90.

55. Torres MJ, Barrionuevo E, Kowalski M, Blanca M. Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs. Immunol Allergy Clin North Am. 2014;34(3):507-24,vii-viii.

56. Ayuso P, Blanca-López N, Doña I, Torres MJ, Guéant-Rodríguez RM, Canto G, et al. Advanced phenotyping in hypersensitivity drug reactions to NSAIDs. Clin Exp Allergy. 2013;43(10):1097-109.

57. Himly M, Jahn-Schmid B, Pittertschatscher K, Bohle B, Grubmayr K, Ferreira F, et al. IgE-mediated immediate-type hypersensitivity to the pyrazolone drug propyphenazone. J Allergy Clin Immunol. 2003;111(4):882-8.

58. Hasan T, Jansen CT. Photopatch test reactivity: effect of photoallergen concentration and UVA dosaging. Contact Dermatitis. 1996;34(6):383-6.

59. Zedlitz S, Linzbach L, Kaufmann R, Boehncke WH. Reproducible identification of the causative drug of a fixed drug eruption by oral provocation and lesional patch testing. Contact Dermatitis. 2002;46(6):352-3.

60. Gómez E, Blanca-Lopez N, Torres MJ, Requena G, Rondon C, Canto G, et al. Immunoglobulin E-mediated immediate allergic reactions to dipyrone: value of basophil activation test in the identification of patients. Clin Exp Allergy. 2009;39(8):1217-24.

61. Nizankowska-Mogilnicka E, Bochenek G, Mastalerz L, Swierczyńska M, Picado C, Scadding G, et al. EAACI/GA2LEN guideline: aspirin provocation tests for diagnosis of aspirin hypersensitivity. Allergy. 2007;62(10):1111-8.

62. Berges-Gimeno MP, Simon RA, Stevenson DD. Long-term treatment with aspirin desensitization in asthmatic patients with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. 2003;111(1):180-6.

63. Lee JY, Simon RA, Stevenson DD. Selection of aspirin dosages for aspirin desensitization treatment in patients with aspirinexacerbated respiratory disease. J Allergy Clin Immunol. 2007;119(1):157-64.

64. Comert S, Celebioglu E, Yucel T, Erdogan T, Karakaya G, Onerci M, et al. Aspirin 300 mg/day is effective for treating aspirin-exacerbated respiratory disease. Allergy. 2013;68(11):1443-51.


Submitted date:
05/12/2015

Accepted date:
05/16/2015

6a75ea86a953955a5c60e1dd 1776695468 Articles
Links & Downloads

Arq Asma Alerg Imunol

Share this page
Page Sections